7 Rapid Virological Response Is a More Important Predictor of Sustained Virological Response (Svr) Than Genotype in Patients With Chronic Hepatitis C Virus Infection

Fried, M.W.; Hadziyannis, S.; Shiffman, M.; Messinger, Diethelm; Zeuzem, Stefan

doi:10.1016/s0168-8278(08)60009-4

Cited by 29 publications

(32 citation statements)

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“…Thus, the impact of HCV genotype on SVR in the regression models becomes less significant, and viral kinetic parameters are shown to be better than HCV genotype in the prediction of SVR. Therefore, our data suggested that the TT genotype and virion production rate, rather than HCV genotype 1, HCV genotype 2, or the virion clearance rate, were factors predictive of SVR and strongly supported the concept that viral kinetics or ontreatment HCV RNA levels are the important predictors of SVR in patients with CHC receiving IFN-based therapy (22). Because Han Chinese people are known to have a higher prevalence of the T allele than subjects of European ancestry (International HapMap Project), the different prevalence rates of specific genotypes may partly explain the better virological response in Asian patients with CHC treated with the combination therapy.…”

Section: Discussionsupporting

confidence: 75%

“…Among these factors, viral kinetics following antiviral therapy has become widely accepted in both clinical trials and daily practice (21) and increasingly recognized as the most outweighing predictor of sustained virological response (SVR) to IFN-based therapy (22). Using mathematical models of hepatitis C viral kinetics may further clarify the mechanisms of antiviral therapy, the evolution of resistant viral strains, and the length of time necessary to eradicate the infection (23, 24).…”

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confidence: 99%

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Association of IL28B gene variations with mathematical modeling of viral kinetics in chronic hepatitis C patients with IFN plus ribavirin therapy

Hsu

Chen

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Asian patients with chronic hepatitis C (CHC) are known to have better virological responses to pegylated (Peg) IFN-based therapy than Western patients. Although IL28B gene polymorphisms may contribute to this difference, whether favorable hepatitis C virus (HCV) kinetics during treatment plays a role remains unclear. We enrolled 145 consecutive Taiwanese patients with CHC receiving Peg-IFN α-2a plus ribavirin for the study. Blood samples were taken more frequently at defined intervals in the first 3 d. Peg-IFN was administered at week 1. It was then administered weekly in combination with daily ribavirin for 24 or 48 wk. A mathematical model fitted to the observed HCV kinetics was constructed, which could interpret the transient HCV titer elevation after Peg-IFN treatment. The results demonstrated a comparable viral clearance rate (c = 3.45 ± 3.73) (day −1 , mean ± SD) but lower daily viral production rate (P = 10 6 -10 12 ) in our patients than those reported previously in Western patients. Of 110 patients with a sustained virological response (SVR), 47 (43%) had a transient elevation of viral titer within 12 h (proportion of 12 h/3 d: 44% in non-SVR vs. 70% in SVR; P = 0.029). Among 91 patients with available rs8099917 data, patients with the TT genotype had an early surge of viral titer after therapy and a higher SVR and viral clearance rate than those with the GT genotype. In conclusion, Taiwanese patients with CHC receiving Peg-IFN plus ribavirin therapy have a lower daily viral production rate than Western patients, and the rs8099917 TT genotype may contribute to the increased viral clearance rate and better virological responses in these patients. H epatitis C virus (HCV) infection is the major etiology of chronic liver disease, liver cirrhosis, and hepatocellular carcinoma (1, 2). According to the estimate from the World Health Organization, there are more than 180 million chronic HCV-infected persons worldwide (1-3); hence, effective treatment of chronic hepatitis C (CHC) is important. Nevertheless, the current standard of care for CHC using pegylated (Peg) IFN plus ribavirin is expensive, is effective in only a certain proportion of patients who have CHC, and has many unpleasant adverse effects (4, 5). Therefore, identifying predictive factors of therapeutical response in patients with CHC is important.Several factors have been linked to the therapeutical response of patients who have CHC, including viral factors (6-11), host factors (12-15), metabolic factors (16-18), histological factors (19), types of regimen (4), and duration of infection (20). Among these factors, viral kinetics following antiviral therapy has become widely accepted in both clinical trials and daily practice (21) and increasingly recognized as the most outweighing predictor of sustained virological response (SVR) to IFN-based therapy (22). Using mathematical models of hepatitis C viral kinetics may further clarify the mechanisms of antiviral therapy, the evolution of resistant viral strains, and the length of time necessary to er...

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Section: Discussionsupporting

confidence: 75%

mentioning

confidence: 99%

Association of IL28B gene variations with mathematical modeling of viral kinetics in chronic hepatitis C patients with IFN plus ribavirin therapy

Hsu

Chen

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…13,[27][28][29] The results of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial in the United States were recently published. 13 The primary endpoint of this trial was the progression of liver disease (as indicated by death, hepatocellular carcinoma, hepatic decompensation, or for patients with bridging fibrosis at baseline, an increase in the Ishak fibrosis score of !2 points) within 3.8 years after randomization to lowdose peginterferon alfa-2a therapy or no treatment.…”

mentioning

confidence: 99%

Histologic Outcomes in Hepatitis C–Infected Patients with Varying Degrees of Virologic Response to Interferon-Based Treatments

Pockros

Hamzeh²,

Martin

et al. 2010

Hepatology

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Patients with chronic hepatitis C with partial virologic response or nonresponse to interferon‐based therapies can experience treatment‐related improvements in liver histology. This retrospective analysis assessed the histologic response to treatment in patients with varying degrees of virologic response (sustained virologic response [SVR], breakthrough, relapse, or nonresponse), time to hepatitis C virus (HCV) RNA undetectability, and duration of viral suppression. Patients (HCV genotypes 1‐6) with baseline and follow‐up liver biopsies from eight phase 2 to phase 4 interferon‐based trials were analyzed. Blinded biopsies were evaluated by a single pathologist. Improvements or worsening of METAVIR necroinflammatory activity and fibrosis were defined as increase or decrease of ≥1 grading category from baseline to 24 weeks after end of treatment. A majority of the 1571 patients with paired biopsy data were white, male, with HCV genotype 1/4, baseline HCV RNA levels >800,000 IU/mL, and baseline alanine aminotransferase levels ≤3 × upper limit of the normal range; mean baseline activity and fibrosis scores were 1.8 and 1.7, respectively. Overall, 80% of patients received peginterferon alfa‐2a monotherapy or peginterferon alfa‐2a/ribavirin combination therapy. Mean treatment duration was 46 weeks. There was a positive correlation between the degree of virologic response and improvements in METAVIR activity and fibrosis, and an inverse correlation with worsening activity and fibrosis (all comparisons, P < 0.0001). Patients with SVR had the greatest histologic benefit. As a combined group, relapsers and patients with breakthrough had significantly greater benefits than nonresponders (activity, P = 0.0001; fibrosis, P = 0.003). Consistent with these results, a better histologic response was correlated with a shorter time to undetectable HCV RNA and a longer duration of viral suppression (all comparisons, P < 0.0001). Conclusion: In patients with chronic hepatitis C who were treated with interferon‐based therapies, histologic benefits may be observed even in the absence of an SVR. (HEPATOLOGY 2010;)

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“…Biohemijska procena podrazumeva normalizaciju aktivnosti transaminaza (ALT), a histološka sa zloupotrebom narkotika i alkohola i dr. Na osnovu faktora, koji pozitivno utiču na efikasnost terapije, moguće je predvideti postizanje SVR. To su: ženski pol, životno doba (<40 god), G2 i G3, niska viremija pre terapije, brzi virusološki odgovor, odsustvo ciroze, steatoze jetre, gojaznosti, komorbiditeta, zloupotrebe alkohola i koinfekcija (HBV, HIV) [2,3,[6][7][8][9][10][11][12][13][14][15]. Ukupna doza primljenog RBV utiče na postizanje SVR i relaps.…”

Section: Uvodunclassified

“…Za razliku od njih kod bolesnika bez postignutog EVR samo je kod 14% terapija bila uspešna, odnosno postignut je SVR. Naši podaci u pogledu predviđanja postizanja SVR na osnovu EVR su u skladu sa podacima drugih ispitivanja [8,9,[11][12][13]30].…”

Section: Diskusijaunclassified

Savremena terapija hroničnog hepatitisa C: efikasnost i mogućnost predviđanja terapijskog odgovora

Bozic

Bojović

Đonić-Nenezić

et al. 2011

BII

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1Klinika za infektivne i tropske bolesti Kliničkog centra Srbije, Beograd Uvod. Hepatitis C virus (HCV) je jedan od glavnih uzročnika hroničnog hepatitisa, ciroze jetre i hepatocelularnog karcinoma (HCC). Savremena terapija hroničnog hepatitisa C (HHC) podrazumeva primenu pegilovanog interferona alfa 2a ili 2b (PEG IFN-α2a ili PEG IFN-α2b) i ribavirina (RBV). Cilj rada je da se proceni efikasnost HCV terapije i faktora za predviđanje terapijskog odgovora. Rezultati. U grupi bolesnika sa HHC više je bilo muškaraca (59,3%), starijih od 40 godina (58,2%), sa visokim stepenom bazalne viremije (63%) i sa G1 (67%) HCV. Bridging fibroza i ciroza (F3, F4) su nađene kod 54 (27, 84%) bolesnika. Stabilan virusološki odgovor (SVR) je postignut kod 69,2%, relaps kod 11,9%, a bez odgovora na terapiju je bilo 19,8% bolesnika. Faktori koji su uticali na postizanje SVR bili su: non-1 genotip HCV (OR 5,9; 95% IP: 1,9-18,0), EVR (OR 0,92,; 95% IP: 2,73-35,97) i bolesnici mlađi od 40 godina (OR 3,66; 95% IP: 1,48-9,0). Neuspeh terapije u vidu relapsa zavisio je od visine bazalne viremije (OR 0,37; 95% IP: 0,12-0,97), godina života >40 godina (OR 4,8; 95% IP: 1,35-17,84) i prisustva ciroze (OR 2,1; 95% IP: 1,0-4,7). Kod bolesnika bez odgovora na terapiju faktori predviđanja neuspeha su bili: G1 (OR 3,9; 95% IP: 1,5-10,3), visoka bazalna viremija (OR 3,45; 95% IP: 1,19) i prekid u kontinuitetu primene terapije (OR 4,49; 95% IP: 1,76).Zaključak. Savremena, standardna terapija je bila efikasna kod 127/194 (69,2%) bolesnika sa HCC. Najznačajniji faktori za predviđanje uspeha terapije bili su: genotip HCV, EVR kod G1, životno doba bolesnika, stepen bazalne viremije, prisustvo ciroze i prekid u kontinuitetu terapije.Ključne reči: hronični hepatitis C, efikasnost antivirusne terapije, predviđanje virusološkog odgovora.

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7 Rapid Virological Response Is a More Important Predictor of Sustained Virological Response (Svr) Than Genotype in Patients With Chronic Hepatitis C Virus Infection

Cited by 29 publications

References 0 publications

Association of IL28B gene variations with mathematical modeling of viral kinetics in chronic hepatitis C patients with IFN plus ribavirin therapy

Association of IL28B gene variations with mathematical modeling of viral kinetics in chronic hepatitis C patients with IFN plus ribavirin therapy

Histologic Outcomes in Hepatitis C–Infected Patients with Varying Degrees of Virologic Response to Interferon-Based Treatments

Savremena terapija hroničnog hepatitisa C: efikasnost i mogućnost predviđanja terapijskog odgovora

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